Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Blood. 2011 Apr 7;117(14):3921-8. doi: 10.1182/blood-2010-10-311894. Epub 2011 Feb 3.
Hastening posttransplantation immune reconstitution is a key challenge in human leukocyte antigen (HLA)-haploidentical hematopoietic stem-cell transplantation (HSCT). In experimental models of mismatched HSCT, T-regulatory cells (Tregs) when co-infused with conventional T cells (Tcons) favored posttransplantation immune reconstitution and prevented lethal graft-versus-host disease (GVHD). In the present study, we evaluated the impact of early infusion of Tregs, followed by Tcons, on GVHD prevention and immunologic reconstitution in 28 patients with high-risk hematologic malignancies who underwent HLA-haploidentical HSCT. We show for the first time in humans that adoptive transfer of Tregs prevented GVHD in the absence of any posttransplantation immunosuppression, promoted lymphoid reconstitution, improved immunity to opportunistic pathogens, and did not weaken the graft-versus-leukemia effect. This study provides evidence that Tregs are a conserved mechanism in humans.
加速移植后免疫重建是人类白细胞抗原（HLA）单倍体造血干细胞移植（HSCT）的一个关键挑战。在错配 HSCT 的实验模型中，T 调节细胞（Tregs）与常规 T 细胞（Tcons）共同输注时，有利于移植后免疫重建，并防止致命的移植物抗宿主病（GVHD）。在本研究中，我们评估了在 28 例高危血液恶性肿瘤患者中，早期输注 Tregs 后再输注 Tcons 对预防 GVHD 和免疫重建的影响，这些患者接受了 HLA 单倍体 HSCT。我们首次在人类中证明，Tregs 的过继转移可在没有任何移植后免疫抑制的情况下预防 GVHD，促进淋巴细胞重建，改善对机会性病原体的免疫力，并且不会削弱移植物抗白血病效应。这项研究提供了证据表明 Tregs 是人类中保守的机制。
